Pulmonary, Critical Care, and Sleep Medicine

Oct. 15, 2019

Fibrosing mediastinitis (FM) represents a fibroinflammatory disease involving the mediastinum and hilar areas. It is characterized by expansive growth of fibroinflammatory tissue within this space, resulting in narrowing and obstruction of vital vascular structures such as the superior vena cava, pulmonary arteries and veins; airways; or the esophagus. The disease primarily presents in younger patients and relentless disease progression has been associated with a high mortality.

While in most cases FM is thought to represent an idiosyncratic response to an external antigen ― in North America, the antigen is most commonly histoplasmosis ― idiopathic cases can also occur.

"The diagnosis of FM can be very challenging. There is no definitive diagnostic test and tissue biopsies are typically complicated and risky," says Tobias Peikert, M.D., a critical care specialist and pulmonologist at Mayo Clinic in Rochester, Minnesota. "Histoplasmosis-associated FM classically presents as a calcified right-sided mediastinal mass. Clinical symptoms depend on the anatomic structures involved by the process.

"During the diagnostic evaluation, it is crucial to exclude mimics of the disease, including lymphoma, most commonly nodular-sclerosing Hodgkin's disease, other metastatic malignancies, mediastinal granulomatous infections and IgG4-related disease, as noted in studies published in Medicine in 2011 and International Journal of Rheumatology in 2012. PET-CT and targeted invasive tissue biopsies are crucial in patients with nonclassic clinical presentations such as noncalcified, diffuse and bilateral mediastinal infiltration and extrathoracic disease.

"The management of FM is mainly focused on the relieving of vascular and airway obstructions. Surgical interventions are typically avoided and patients are managed with vascular (superior vena cava, pulmonary artery and pulmonary vein) and, less commonly, airway stents, as noted in studies published in the Annals of the American Thoracic Society in 2017 and Catheterization & Cardiovascular Interventions in 2019. These interventions should be primarily driven by patient symptoms.

"Therapeutic responses to systemic therapies such as steroids and antifungal therapy have been very disappointing. However, we have recently started the successful off-label use of rituximab for patients with FM, as noted in the study published in Medicine in 2011 and research published in the American Journal of Respiratory and Critical Care Medicine in 2014.

"We have now treated almost 30 patients with metabolically active (confirmed by PET-CT), progressive FM with rituximab. Disease progression was almost universally halted, 67% of patients improved symptomatically and the noncalcified areas of FM decreased on average by 41%. This extremely exciting data was presented at the 2019 European Respiratory Society International Congress in Madrid."

For more information

Peikert T, et al. Fibrosing mediastinitis: Clinical presentation, therapeutic outcomes, and adaptive immune response. Medicine. 2011;90:412.

Peikert T, et al. Histopathologic overlap between fibrosing mediastinitis and IgG4-related disease. International Journal of Rheumatology. 2012;207056.

Kern R, et al. Bronchoscopic management of airway compression due to fibrosing mediastinitis. Annals of the American Thoracic Society. 2017;14:1353.

Fender EA, et al. Catheter based treatments for fibrosing mediastinitis. Catheterization & Cardiovascular Intervention. In press.

Westerly BD, et al. Targeting B lymphocytes in progressive fibrosing mediastinitis. American Journal of Respiratory and Critical Care Medicine. 2014;190:1069.

ERS International Congress 2019. European Respiratory Society.